The role of structural disorder in the function of RNA and protein chaperones

Peter Tompa, Peter Csermely

Research output: Contribution to journalReview article

401 Citations (Scopus)

Abstract

Chaperones are highly sophisticated protein machines that assist the folding of RNA molecules or other proteins. Their function is generally thought to require a fine-tuned and highly conserved structure: despite the recent recognition of the wide-spread occurrence of structural disorder in the proteome, this structural trait has never been generally considered in molecular chaperones. In this review we give evidence for the prevalence of functional regions without a well-defined 3-D structure in RNA and protein chaperones. By considering a variety of individual examples, we suggest that the structurally disordered chaperone regions either function as molecular recognition elements that act as solubilizers or locally loosen the structure of the kinetically trapped folding intermediate via transient binding to facilitate its conformational search. The importance of structural disorder is underlined by a predictor of natural disordered regions, which shows an extremely high proportion of such regions, unparalleled in any other protein class, within RNA chaperones: 54.2% of their residues fall into disordered regions and 40% fall within disordered regions longer than 30 consecutive residues. Structural disorder also prevails in protein chaperones, for which frequency values are 36.7% and 15%, respectively. In keeping with these and other details, a novel "entropy transfer" model is presented to account for the mechanistic role of structural disorder in chaperone function.

Original languageEnglish
Pages (from-to)1169-1175
Number of pages7
JournalFASEB Journal
Volume18
Issue number11
DOIs
Publication statusPublished - Aug 1 2004

Keywords

  • Chaperone evolution
  • Chaperone function
  • Entropy transfer
  • Intrinsically unstructured protein

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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